The overall goal of this proposal is to identify biomarkers in the sputum of patients with emphysema that associate with emphysema but not with either healthy controls, smokers without emphysema, or lung diseases associated with airway inflammation and fibrosis such as asthma or idiopathic pulmonary fibrosis. The approach we plan to use to identify sputum biomarkers in emphysema will use both hypothesis driven experiments to explore candidate sputum biomarkers of inflammation (LTB4, IL-8, TNF), fibrosis (TGF- beta, PGDF, FGF), metalloproteases (MMP-1, MMP-9, MMP-12, TIMP), elastin degradation (desmosine in urine) as well as an alternative approach using both proteomic analysis of sputum and bronchoalveolar lavage, and genomic studies of airway epithelium and alveolar macrophages to identify potential novel biomarkers of emphysema that correlate with CT scan evidence of emphysema. Levels of biomarkers will be measured over a two year period and be correlated with CT scan extent of emphysema. If such a non-invasive biomarker were identified this could either serve as a biomarker in studying the effects of intervention with anti-inflammatory medications or smoking cessation in subjects with emphysema, or alternatively serve to identify smokers at risk for the development of emphysema.